Scavenger receptors (SRs), commonly expressed on the surfaces of phagocytes, are a structurally diverse group of receptors that share a common theme of binding to modified lipoproteins. Biologically, SRs are important for the detection and clearance of a wide array of potentially harmful ligands such as oxidatively modified proteins and lipoproteins, advanced glycation end products (AGE), oxidatively modified phospholipids, bacterial DNA, anionic polymers, apoptotic cells, bacterial cell wall components, and foreign particles such as silica dust and asbestos. Particular attention has been focused on oxidized low density lipoprotein (oxLDL), an SR ligand thought to be significant in the pathology of atherosclerosis, oxLDL-binding SRs and on SRs involved in the transport of lipids across the cell membrane. We have begun structural investigations of three key SRs important in both of these areas in addition to a protein SR ligand involved in antigen presentation. Our goal is to analyze these receptors and receptor/ligand complexes by x-ray crystallography as a means to understand the mechanisms of ligand recognition and subsequent signal transduction through the plasma membrane. This information is critical to elucidating how phagocytes interface with and respond to both endogenous and environmental challenges. Subcloning, design of multiple constructs, and receptor expression studies in E coli are currently underway.